Chronic Acidosis Research Articles

Zootechnical Additives for Optimum Production in Livestocks in Stallfed Condition

This is the point of interest to use zootechnical additives in ruminants to control the accumulation of lactate in the rumen. The primary and main cause of acidosis is due to consumption of rapidly digestible carbohydrate in high amount. In normal animal husbandry (stall fed) practices generally livestock are feed with the left out or waste products rich in carbohydrates. This excessive carbohydrate consumption leads to sudden change in ruminal environment, causing sub-acute or chronic lactic acidosis. The ruminal lactic acidosis problem can be averted by either zootechnic additives such as Saccharomyces cereviseae and Megasphaera elsdenii or adding sodium bicarbonate/enzymes in feed or ration.

Exploring the Prevalence of Respiratory Failure in Adults Presenting With Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) poses a significant global health burden and is a leading cause of morbidity and mortality. Acute exacerbations of COPD often lead to respiratory failure, necessitating a thorough understanding of its prevalence. This study aimed to investigate the prevalence of respiratory failure among adult patients experiencing acute exacerbations of COPD. A descriptive, cross-sectional study was conducted over a span of seven months at the internal medicine department of Hayatabad Medical Complex, Peshawar. A total of 255 adult patients with acute exacerbations of COPD were included, and their demographic data, as well as arterial blood gas (ABG) analysis results, were collected. The prevalence of respiratory failure was defined by specific arterial blood gas criteria. The study revealed a notable prevalence of respiratory failure (41.18%) among COPD patients presenting with acute exacerbations. Factors such as older age and male gender were identified as being associated with a heightened risk of respiratory failure. In conclusion, acute exacerbations of COPD predominantly affect middle-aged males (65.5%), with the 51-60 age group being the most impacted. Respiratory failure was present in over 41% of cases. ABG analysis indicated significant acid-base imbalances, hypoxemia, and hypercapnia, with compensatory chronic respiratory acidosis. These findings highlight the need for targeted interventions to manage and prevent COPD exacerbations, especially in middle-aged men.

Characteristics of pulse oximetry and arterial blood gas in patients with fibrotic interstitial lung disease

BackgroundFibrotic interstitial lung disease (ILD) is frequently associated with abnormal oxygenation; however, little is known about the accuracy of oxygen saturation by pulse oximetry (SpO2) compared with arterial blood gas...

Impact of Acute or Chronic Acidosis and Hypoxia on Gene Expression Patterns in Tumour Cells: Potential Functional Implications.

Tumours often exhibit pronounced hypoxia and hereby extracellular acidosis due to intensified glycolysis. Since metabolic parameters can modulate gene expression, the aim of the study was to analyse changes in gene expression patterns induced by acute (24h) acidosis or hypoxia and also in tumour cells adapted to long-term acidosis (5weeks). Three tumour cell lines (AT1 prostate carcinoma, MCF-7, and MDA-MB-231 breast carcinoma) were exposed to acidosis (pH6.6) or hypoxia (pO2 1.5mmHg) for 24h. For long-term acidosis, AT1 tumour cells were continuously cultured at pH6.6 for 5weeks. Gene expression was examined by total RNA-sequencing and the functional significance was assessed by gene set enrichment analysis using the Gene Ontology database. Under short-term acidosis (24h), AT1 and MCF-7 cells showed comparable changes. 714 genes were acidosis-dependently regulated in AT1 cells (275 up, 439 down), and 221 genes in MCF-7 cells (95 up, 126 down). MDA-MB-231 cells almost did not respond to low pH (13 regulated genes). Hypoxia affected MCF-7 cells the most (1498 regulated genes), whereas fewer genes were regulated in AT1 and MDA-MB-231 cells. Concerning the function of the regulated genes by short-term acidosis, RNA processing, cell cycle regulation, DNA synthesis, and mitochondrial function were negatively affected. Chronic acidosis showed a different picture. In AT1 cells, 1160 genes were differentially expressed (638 up, 522 down) when cells exposed to low pH for 5weeks. The putatively acidosis-induced changes in functions included tissue structural development, RNA processing, and mitochondrial activity. This study shows that both acute and chronic acidosis of tumour cells lead to altered gene expression and thus affect cell function. Long-term acidosis leads to fundamentally different changes, indicating an adaptation process of the tumour cells.

Primary Sjogren’s syndrome with secondary distal renal tubular acidosis unmasked during pregnancy: A rare presentation

ABSTRACT Renal tubular acidosis (RTA) comprises transport defects in renal reabsorption of bicarbonate, impaired acidification of urine, or both. It is broadly classified into distal, proximal, and hyperkalemic RTA. Distal RTA (dRTA) is characterized by reduced net acid excretion in urine. It can be primary or secondary, and hypokalemia is often a central presenting feature. Hypokalemia may present with flaccid quadriparesis, arrhythmia, and respiratory failure. Hypokalemia also causes nephrogenic diabetes insipidus (NDI) due to the downregulation of vasopressin-responsive aquaporin-2 water channel and inhibition of renal response to vasopressin. Primary Sjogren’s syndrome (pSS) is the most common autoimmune disorder associated with secondary dRTA. Here, we present the case of a 22-year-old critically ill pregnant lady with adverse pregnancy outcomes, diagnosed to be pSS with dRTA, who presented with severe hypokalemia and hypernatremia (due to NDI). Both pSS and chronic acidosis are associated with adverse pregnancy outcomes.

Effect of the Sr-Fe layered double hydroxide coating based on the microenvironment response on implant osseointegration in osteoporotic rats.

Osteoporosis is a disease that manifests itself as an abnormality of bone metabolism and is characterized by low bone mass and destruction of the bone microstructure. Since bone resorption occurs more rapidly than new bone formation, osteoporosis leads to reduced orthopedic implant stability. From a microenvironmental point of view, the rationale for this outcome is that osteoclasts are overactive in the bone tissue of patients with osteoporosis, and the large amount of H+ they produce leads to local chronic acidosis, which promotes bone mineral loss. Therefore, we designed a weakly alkaline layered double hydroxide (LDH) coating to modulate the pathologically acidic microenvironment and the osteogenic-osteoclastic coupling by releasing Sr2+. We prepared Sr-Fe LDH coatings on pure titanium implants using a hydrothermal method in this study and characterized the material using SEM, AFM, XRD, XPS, EDS, ICP, pH acidimeter, etc. We found that the coatings had good nanomorphology and were able to efficiently neutralize H+ as well as steadily release Sr2+ for up to 21 days. In vitro, the coating not only significantly promoted the adhesion, proliferation, and differentiation of osteoblasts, but also inhibited the differentiation of osteoclasts at the same time. In addition, in animal experiments, the coating significantly improved the mechanical stability of the implant in osteoporotic rats, increasing Sr-Fe LDH@Ti maximal push-out force by 72.2% compared to Ti. At the same time, the coating was effective in reversing the osteoporotic state, resulting in a 58.5% increase in BV/TV (%), and a 12.4% increase in Tb. N (1 mm-1), a 31.6% increase in Tb. Th (μm), and a 30.9% increase in BA (%). Our results suggest that this Sr-Fe LDH nanocoating material with acid-neutralizing, as well as long-term Sr2+-releasing capabilities, is a novel and effective orthopedic implant coating material under osteoporotic conditions.

#3827 BICARBONATE PROFILING IN HEMODIALYSIS: MATHEMATICAL MODELING OF DATA FROM A CLINICAL TRIAL

Abstract Background and Aims During hemodialysis (HD), bicarbonate and other bases are added to the dialysis fluid to correct chronic acidosis that may develop in kidney-impaired patients, increasing plasma bicarbonate concentration to physiological levels. Previous studies have shown that both exceedingly high and low post-dialysis bicarbonate concentrations are associated with adverse clinical outcomes; however, no clear guidelines for the prescription of bicarbonate concentration in the dialysis fluid are available. Data from a recent controlled clinical trial, carried out at the Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw (Poland), were used to identify transport parameters of a mathematical model of acid-base homeostasis in HD patients, as the first step in the implementation of a tool to optimize bicarbonate profiling during HD. Method The study was carried out in 20 chronic patients, undergoing thrice weekly 4-hr HD. The patients underwent three treatment regimens: A) constant dialysis fluid bicarbonate concentration (HCO3,D) equal to 35 mEq/L; B) HCO3,D decreasing from 35 to 30 mEq/L after 2 hrs; C) HCO3,D increasing from 30 to 35 mEq/L after 2 hrs. The patients were divided in two cohorts: for the first (n = 11) treatment schedule was: treatment A during the first and third week, B during the second week and C during the fourth week. For the second cohort (n = 9) treatment C was carried out during the second week and treatment B during the fourth. Data were collected only during the second and third sessions of the week, and acid-base composition was determined using a blood gas analyzer. The mathematical model describes the transport of bicarbonate and dissolved CO2 from dialysis fluid to the patient and can predict changes in the acid-base equilibrium of arterial and venous plasma and erythrocytes, interstitial fluid, and tissue cells, using mass transport equations. The dialysances for bicarbonate (KHCO3) and dissolved CO2 (KCO2) were estimated via least square minimization. Results No significant difference was found comparing patients in the two cohorts, or comparing sessions of the same week. Pre-dialysis plasma bicarbonate, pH, or CO2 partial pressure (PCO2) were significantly lower for treatment B compared to treatment A. Average plasma bicarbonate concentrations for the different treatments are shown in Figure 1 for data and model simulations. Table 1 reports the average values of the estimated parameters for week. No statistically significant difference was found between sessions, cohorts, or treatments. The model fitted bicarbonate data with an average error of 2.5 ± 1.4%, and PCO2 with an error of 4.5 ± 3.6%. Simulations of mixed-venous blood, interstitial fluid, and tissue cells concentrations showed a similar response to different treatments as in arterial blood. Conclusion The model accurately describes plasma bicarbonate data with high accuracy regardless of the treatment conditions. The parameters estimated showed considerable variability between treatments (less so between the sessions of the same week), but without statistical significance. The model can be used to simulate the effect of dialysate bicarbonate profiling on acid-base equilibrium in HD patients.

Acid-adapted cancer cells alkalinize their cytoplasm by degrading the acid-loading membrane transporter anion exchanger 2, SLC4A2

Acidic environments reduce the intracellular pH (pHi) of most cells to levels that are sub-optimal for growth and cellular functions. Yet, cancers maintain an alkaline cytoplasm despite low extracellular pH (pHe). Raised pHi is thought to be beneficial for tumor progression and invasiveness. However, the transport mechanisms underpinning this adaptation have not been studied systematically. Here, we characterize the pHe-pHi relationship in 66 colorectal cancer cell lines and identify the acid-loading anion exchanger 2 (AE2, SLC4A2) as a regulator of resting pHi. Cells adapt to chronic extracellular acidosis by degrading AE2 protein, which raises pHi and reduces acid sensitivity of growth. Acidity inhibits mTOR signaling, which stimulates lysosomal function and AE2 degradation, a process reversed by bafilomycin A1. We identify AE2 degradation as a mechanism for maintaining a conducive pHi in tumors. As an adaptive mechanism, inhibiting lysosomal degradation of AE2 is a potential therapeutic target.

Chronic acidosis rewires cancer cell metabolism through PPARα signaling.

The mechanisms linking tumor microenvironment acidosis to disease progression are not understood. Here, we used mammary, pancreatic, and colon cancer cells to show that adaptation to growth at an extracellular pH (pHe ) mimicking acidic tumor niches is associated with upregulated net acid extrusion capacity and elevated intracellular pH at physiological pHe , but not at acidic pHe . Using metabolic profiling, shotgun lipidomics, imaging and biochemical analyses, we show that the acid adaptation-induced phenotype is characterized by a shift toward oxidative metabolism, increased lipid droplet-, triacylglycerol-, peroxisome content and mitochondrial hyperfusion. Peroxisome proliferator-activated receptor-α (PPARA, PPARα) expression and activity are upregulated, at least in part by increased fatty acid uptake. PPARα upregulates genes driving increased mitochondrial and peroxisomal mass and β-oxidation capacity, including mitochondrial lipid import proteins CPT1A, CPT2 and SLC25A20, electron transport chain components, peroxisomal proteins PEX11A and ACOX1, and thioredoxin-interacting protein (TXNIP), a negative regulator of glycolysis. This endows acid-adapted cancer cells with increased capacity for utilizing fatty acids for metabolic needs, while limiting glycolysis. As a consequence, the acid-adapted cells exhibit increased sensitivity to PPARα inhibition. We conclude that PPARα is a key upstream regulator of metabolic changes favoring cancer cell survival in acidic tumor niches.

Case of Chronic Lactic Acidosis in an Adult Female

Case of Chronic Lactic Acidosis in an Adult Female

Nodular-like glomerular lesion after long-standing chronic renal infection in a patient with medullary sponge kidney and mild hyperglycemia

A 63-year-old Japanese woman was admitted to our institute for the evaluation of proteinuria. The patient was diagnosed with medullary sponge kidney, distal type renal tubular acidosis, and renal infection at the age of 37. Thereafter, the patient had repeated renal infections. Urinary proteinuria appeared at around the age of 61 and gradually increased up to 1.0 g daily. In the same period, glycated hemoglobin (HbA1c) increased to 7.0%. On kidney biopsy, light microscopy showed a nodular glomerular lesion and capsular drop. Linear staining for immunoglobulin G along the glomerular basement membrane was observed by immunofluorescence. Electron microscopy showed thickening of the glomerular basement membrane to a width of 800–900 nm. A class III glomerular lesion was diagnosed according to the Tervaert classification. This case indicates that mild but prolonged hyperglycemia for more than 10 years may also contribute to the formation of nodular lesions, although long-standing repeated chronic renal infection and chronic acidosis may have been a precipitating factor in the formation of diabetic nephropathy, including nodular glomerular lesions. This hypothesis is of interest because nodular lesions specific to diabetes are currently considered to be associated with long-term severe hyperglycemia. Learning points Nodular glomerular lesions in diabetes mellitus are thought to be associated with long-term severe hyperglycemia. This case shows that although mild, long-term hyperglycemia for more than 10 years may also contribute to the formation of nodular lesions and that repeated chronic kidney infections over the years and chronic acidosis may be facilitating factors in the formation of diabetic nephropathy, including nodular glomerular lesions. This case appears to be idiopathic nodular glomerulosclerosis of the medullary sponge kidney associated with chronic urinary tract infection.

39-Year-Old Woman With Severe Weakness

39-Year-Old Woman With Severe Weakness

Acidosis regulation of epithelial barrier function and immune signaling

A common but often underappreciated aspect of the inflammatory microenvironment is extracellular acidification. As with other chronic inflammatory diseases, tissue acidification has been observed in inflammatory bowel disease (IBD) patients. Colonic pH as low as 4 have been reported in IBD patients. In contrast, the pH of a healthy colon is between a pH of 7.0‐7.4. Recently, we identified an adaptive tissue response in intestinal epithelial cells (IEC) which buffered extracellular acidification during neutrophil transepithelial migration, suggesting pH homeostasis is an important aspect of acute inflammation. Extensions of these studies identified a previously undescribed CREB‐dependent pathway for sensing extracellular pH and a unique acidosis gene signature in IEC. The full impact of acidosis on IEC function remains unclear. To better understand the impact of chronic extracellular acidification on IEC function, we investigated changes in IEC immune signaling and barrier function in the setting of acute and chronic exposure to acidosis. We initially examined barrier function in T84 IEC cultured under acidic conditions and observed a significant decrease in barrier function, as determined by transepithelial electrical resistance (TER) and paracellular flux, in cells exposed to acidosis in a pH range of 6.0 – 7.4. Interestingly, following acute acidification, treatment with low pH for less than 8hr, barrier function recovered within 16hr. However, following chronic acidification, treatment with low pH beyond 16hr resulted in an appreciable barrier dysfunction for several days. We extended these studies to examine expression and localization of tight‐junction proteins in IEC exposed to acidosis and observed a time and dose‐dependent decrease in ZO‐1 and E‐cadherin expression, with almost complete loss of expression after 72hr at a pH of 6.0. Likewise, expression and localization of claudins 1, 2, and 4 decreased over time. In parallel to a loss of barrier function, IEC exposed to chronic acidosis revealed a prominent increase in the expression of inflammatory markers including several chemokines (IL‐8, CCL20, TNF) as well as anti‐microbial peptides (mucins and beta‐defensins).Thus, chronic extracellular acidosis induces the loss of IEC tight junction function, while inducing the expression of several pro‐inflammatory chemokines and the production of various anti‐microbial peptides. These results identify extracellular acidification as significant signaling mechanism which induces a loss of epithelial features and the acquisition of a more immune‐like phenotype. Furthering our understandings of the mechanisms involved in acidosis induced phenotype switching in IEC has the potential to uncover novel therapeutic drug targets.

Enhanced pentose phosphate pathway activity promotes pancreatic ductal adenocarcinoma progression via activating YAP/MMP1 axis under chronic acidosis.

Background: Acidic microenvironment is a common physiological phenomenon in tumors, and is closely related to cancer development, but the effects of acidosis on pancreatic adenocarcinoma (PDAC) remains to be elucidated.Methods: Metabonomic assay and transcriptomic microarray were used to detect the changes of metabolites and gene expression profile respectively in acidosis-adapted PDAC cells. Wound healing, transwell and in vivo assay were applied to evaluate cell migration and invasion capacity. CCK8 and colony formation assays were performed to determine cell proliferation.Results: The acidosis-adapted PDAC cells had stronger metastasis and proliferation ability compared with the control cells. Metabonomic analysis showed that acidosis-adapted PDAC cells had both increased glucose and decreased glycolysis, implying a shift to pentose phosphate pathway. The metabolic shift further led to the inactivation of AMPK by elevating ATP. Transcriptomic analysis revealed that the differentially expressed genes in acidosis-adapted cells were enriched in extracellular matrix modification and Hippo signaling. Besides, MMP1 was the most upregulated gene in acidosis-adapted cells, mediated by the YAP/TAZ pathway, but could be reduced by AMPK activator.Conclusion: The present study showed that metabolic reprogramming promotes proliferation and metastasis of acidosis-adapted PDAC cells by inhibiting AMPK/Hippo signaling, thus upregulating MMP1.

Abstract 9359: Intrarenal Release of Superoxide Act Synergistically With Interstitial Angiotensin II to Promote Hypertension During Chronic Acidotic Conditions

The capacity of chronic metabolic acidosis (CMA) to evoke hypertension has been previously evaluated. The superoxide mediated oxidative stress and the activation of intrarenal angiotensin II (Ang II), demonstrated a potential role in the pathogenesis of hypertension during CMA involving renal tubular sodium retention leading to volume expansion and strain to blood vessels. The primary focus of the present study was to determine whether the superoxide and the renal angiotensin II acts either synergistically or independently of each other to promote hypertension and the underlying mechanism of superoxide generation. Male Sprague Dawley Rats (100-150gms) were divided into four groups. Chronic acidosis was induced in all 4 groups by providing free access to ammonium chloride solution (0.28M) for 8 weeks in the drinking water. The second, third, and fourth groups were injected daily with captopril (12 mg/kg/day), tempol (100μmol/kg/day) and captopril+tempol respectively. After 8 weeks, blood and urine samples were collected for pH measurements and analyzed for sodium and potassium levels. Rats were anesthetized and in-line mean arterial pressure were determined. The renal cortical tissue homogenates from all four groups were analyzed for superoxide dismutase (SOD) and NADPH oxidase (NOX2) expression. Mean arterial pressure is significantly decreased in fourth group compared to the second and third groups. The serum sodium levels in fourth group were significantly reduced compared to the separately treated second and third groups, which suggested the declined reabsorption of sodium as the cause of decreased blood pressure in the fourth group. On the other hand, there was an increased SOD activity in the fourth group compared to the second and third groups, which implied intrarenal Ang II reduces the release of superoxide by increasing its dismutation. Moreover, our results demonstrated that there were no significant alterations in phagocytic NOX2 protein levels in all four treatment groups, which indicated that the superoxide release could be due to mitochondrial oxidative stress. Overall, blocking the release of intrarenal Ang II along with promoting the superoxide dismutation, showed a potential combined effect to control the observed hypertension.

INFLUENCE OF CHRONIC NON-GASEOUS ACIDOSIS ON BONE TISSUE

The urgency of the problem is due to the high prevalence among the population in all countries of the world and socio-economic losses associated with serious complications of osteoporosis. Chronic non-gaseous acidosis leads to disruption of many metabolic processes, which causes dysfunction of some organs, namely, can lead to decreased kidney function, exacerbate cardiovascular disease, the development of osteoporosis. Different types of non-gaseous acidosis are accompanied by changes in protein metabolism, which lead to the development of osteoporosis.
 Aim: to study the structural features of the bone tissue of the femur in chronic non-gaseous acidosis.
 Methods. The experiments were carried out on 60 intact white outbred male rats weighing 120-180 g, which were kept on a balanced diet of vivarium. Chronic non-gaseous acidosis was simulated by daily intragastric administration with a probe for 60 days 20 mmol/kg NH4CL. The control animals were injected with the same amount of tap water. Histological examination and osteometry were used to study the structure, length and thickness of the rat femur. Free, bound, and total oxyproline in rat urine was determined by biochemical method.
 Results. In chronic non-gaseous acidosis after 6 months there is a tendency to reduce the length and thickness of the femur, but does not differ significantly from the control group. In the urine of rats of the experimental group, the total oxyproline increases mainly due to an increase in free oxyproline, which indicates the predominance of collagen degradation over repair. The histological structure of the bone is disturbed due to the thinning of the bone beams, the intercellular matrix is disorganized, in some places there is its "defibering" with the formation of foci of destruction and cylindrical "lumens". There is a violation of the crystalline structure of bone tissue, its uneven calcification, the formation of cracks in the bone beams.
 Studied literature sources and our research indicate that chronic non-gaseous acidosis has a pathogenic effect on the histological structure of bone. Acidosis is a stress factor that increases the level of glucocorticoids. Glucocorticoids inhibit type I collagen synthesis and increase the expression of collagenase 3, which promotes collagen degradation. Collagen is a source of amino acids that are the substrate for renal ammoniogenesis. Renal ammoniogenesis is a compensatory mechanism in chronic non-gaseous acidosis, which required for restores the normal ratio between fixed cations and anions blood plasma. Thus, the violation of the organic basis of bones is the body's adaptation to chronic non-gaseous acidosis.
 Conclusions. Chronic non-gaseous acidosis simultaneously leads to thinning and disorganization of the intercellular matrix, disruption of the crystal structure of bone tissue, which indicates its important role in the development of osteoporosis. In chronic non-gaseous acidosis, the concentration of oxyproline in the urine increases, which is a marker of the destruction of collagen in the organic matrix of bone.

Functional characterization of the sodium/hydrogen exchanger 8 and its role in proliferation of colonic epithelial cells.

Intestinal NaCl, HCO3-, and fluid absorption are strongly dependent on apical Na+/H+ exchange. The intestine expresses three presumably apical sodium-hydrogen exchanger (NHE) isoforms: NHE2, NHE3, and NHE8. We addressed the role of NHE8 [solute carrier 9A8 (SLC9A8)] and its interplay with NHE2 (SLC9A2) in luminal proton extrusion during acute and chronic enterocyte acidosis and studied the differential effects of NHE8 and NHE2 on enterocyte proliferation. In contrast to NHE3, which was upregulated in differentiated versus undifferentiated colonoids, the expression of NHE2 and NHE8 remained constant during differentiation of colonoids and Caco2Bbe cells. Heterogeneously expressed Flag-tagged rat (r)Nhe8 and human (h)NHE8 translocated to the apical membrane of Caco2Bbe cells. rNhe8 and hNHE8, when expressed in NHE-deficient PS120 fibroblasts showed higher sensitivity to HOE642 compared to NHE2. Lentiviral shRNA knockdown of endogenous NHE2 in Caco2Bbe cells (C2Bbe/shNHE2) resulted in a decreased steady-state intracellular pH (pHi), an increased NHE8 mRNA expression, and augmented NHE8-mediated apical NHE activity. Lentiviral shRNA knockdown of endogenous NHE8 in Caco2Bbe cells (C2Bbe/shNHE8) resulted in a decreased steady-state pHi as well, accompanied by decreased NHE2 mRNA expression and activity, which together contributed to reduced apical NHE activity in the NHE8-knockdown cells. Chronic acidosis increased NHE8 but not NHE2 mRNA expression. Alterations in NHE2 and NHE8 expression/activity affected proliferation, with C2Bbe/shNHE2 cells having lower and C2Bbe/shNHE8 having higher proliferative capacity, accompanied by amplified ERK1/2 signaling pathway and increased EGFR expression in the latter cell line. Thus, both Na+/H+ exchangers have distinct functions during cellular homeostasis by triggering different signaling pathways to regulate cellular proliferation and pHi control.

Gut-kidney axis in oxalate homeostasis.

The gut-kidney axis plays a critical role in oxalate homeostasis, and better understanding of oxalate transport regulatory mechanisms is essential for developing novel therapies. Oxalate potentially contributes to chronic kidney disease (CKD) progression, CKD - and end stage renal disease (ESRD)-associated cardiovascular diseases, polycystic kidney disease (PKD) progression, and/or poor renal allograft survival, emphasizing the need for plasma and urinary oxalate lowering therapies. One promising strategy would be to enhance the bowel's ability to secrete oxalate, which might be facilitated by the following findings. Oxalobacter formigenes (O. formigenes)-derived factors recapitulate O. formigenes colonization effects by reducing urinary oxalate excretion in hyperoxaluric mice by inducing colonic oxalate secretion. Protein kinase A activation stimulates intestinal oxalate transport by enhancing the surface expression of the oxalate transporter SLC26A6 (A6). Glycosylation also stimulates A6-mediated oxalate transport. The colon adapts to chronic acidosis in rats through increased colonic oxalate secretion as previously reported in CKD rats, and A6-mediated enteric oxalate secretion is critical in reducing the body oxalate burden in CKD mice. Intestinal oxalate transport is negatively regulated by proinflammatory cytokines and cholinergic, purinergic, and adenosinergic signaling. These findings could facilitate the development of novel therapeutics for hyperoxalemia, hyperoxaluria, and related disorders if similar regulatory mechanisms are confirmed in humans.

Respiratory Acid-Base Disorders: Respiratory Acidosis and Respiratory Alkalosis

Respiratory acid-base disorders are divided into respiratory acidosis (which can be acute or chronic), and respiratory alkalosis (which also can be acute or chronic). The diagnosis is made after obtaining arterial blood gases (ABGs). Respiratory acidosis is also known as primary hypercapnia and is due to an increase in carbon dioxide (CO2) tension in bodily fluids. The metabolic compensation is an increase in serum bicarbonate (HCO3−), the increase is more pronounced in chronic respiratory acidosis. Oxygen administration (O2) is critical in the management of respiratory acidosis. Respiratory alkalosis or primary hypocapnia is due to a decrease in CO2 tension in bodily fluids. The metabolic compensation is a decrease in HCO3−, the decrease is more pronounced in chronic respiratory alkalosis. Rapid correction of respiratory alkalosis should be avoided, and the underlying etiology should be addressed.

Effect of sodium bicarbonate supplementation on the renin-angiotensin system in patients with chronic kidney disease and acidosis: a randomized clinical trial

BackgroundAcidosis-induced kidney injury is mediated by the intrarenal renin-angiotensin system, for which urinary renin is a potential marker. Therefore, we hypothesized that sodium bicarbonate supplementation reduces urinary renin excretion in patients with chronic kidney disease (CKD) and metabolic acidosis.MethodsPatients with CKD stage G4 and plasma bicarbonate 15–24 mmol/l were randomized to receive sodium bicarbonate (3 × 1000 mg/day, ~ 0.5 mEq/kg), sodium chloride (2 × 1,00 mg/day), or no treatment for 4 weeks (n = 15/arm). The effects on urinary renin excretion (primary outcome), other plasma and urine parameters of the renin-angiotensin system, endothelin-1, and proteinuria were analyzed.ResultsForty-five patients were included (62 ± 15 years, eGFR 21 ± 5 ml/min/1.73m2, plasma bicarbonate 21.7 ± 3.3 mmol/l). Sodium bicarbonate supplementation increased plasma bicarbonate (20.8 to 23.8 mmol/l) and reduced urinary ammonium excretion (15 to 8 mmol/day, both P < 0.05). Furthermore, a trend towards lower plasma aldosterone (291 to 204 ng/L, P = 0.07) and potassium (5.1 to 4.8 mmol/l, P = 0.06) was observed in patients receiving sodium bicarbonate. Sodium bicarbonate did not significantly change the urinary excretion of renin, angiotensinogen, aldosterone, endothelin-1, albumin, or α1-microglobulin. Sodium chloride supplementation reduced plasma renin (166 to 122 ng/L), and increased the urinary excretions of angiotensinogen, albumin, and α1-microglobulin (all P < 0.05).ConclusionsDespite correction of acidosis and reduction in urinary ammonium excretion, sodium bicarbonate supplementation did not improve urinary markers of the renin-angiotensin system, endothelin-1, or proteinuria. Possible explanations include bicarbonate dose, short treatment time, or the inability of urinary renin to reflect intrarenal renin-angiotensin system activity.Graphic abstract